Are Tumor Marker Tests Applied Appropriately in Clinical Practice? A Healthcare Claims Data Analysis.

Tumor markers (TM) are crucial in the monitoring of cancer treatment. However, inappropriate requests for screening reasons have a high risk of false positive and negative findings, which can lead to patient anxiety and unnecessary follow-up examinations. We aimed to assess the appropriateness of TM testing in outpatient practice in Switzerland. We conducted a retrospective cohort study based on healthcare claims data. Patients who had received at least one out of seven TM tests (CEA, CA19-9, CA125, CA15-3, CA72-4, Calcitonin, or NSE) between 2018 and 2021 were analyzed. Appropriate determinations were defined as a request with a corresponding cancer-related diagnosis or intervention. Appropriateness of TM determination by patient characteristics and prescriber specialty was estimated by using multivariate analyses. A total of 51,395 TM determinations in 36,537 patients were included. An amount of 41.6% of all TM were determined appropriately. General practitioners most often determined TM (44.3%) and had the lowest number of appropriate requests (27.8%). A strong predictor for appropriate determinations were requests by medical oncologists. A remarkable proportion of TM testing was performed inappropriately, particularly in the primary care setting. Our results suggest that a considerable proportion of the population is at risk for various harms associated with misinterpretations of TM test results

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

A depauperate immune repertoire precedes evolution of sociality in bees

Background Sociality has many rewards, but can also be dangerous, as high population density and low genetic diversity, common in social insects, is ideal for parasite transmission. Despite this risk, honeybees and other sequenced social insects have far fewer canonical immune genes relative to solitary insects. Social protection from infection, including behavioral responses, may explain this depauperate immune repertoire. Here, based on full genome sequences, we describe the immune repertoire of two ecologically and commercially important bumblebee species that diverged approximately 18 million years ago, the North American Bombus impatiens and European Bombus terrestris. Results We find that the immune systems of these bumblebees, two species of honeybee, and a solitary leafcutting bee, are strikingly similar. Transcriptional assays confirm the expression of many of these genes in an immunological context and more strongly in young queens than males, affirming Bateman’s principle of greater investment in female immunity. We find evidence of positive selection in genes encoding antiviral responses, components of the Toll and JAK/STAT pathways, and serine protease inhibitors in both social and solitary bees. Finally, we detect many genes across pathways that differ in selection between bumblebees and honeybees, or between the social and solitary clades. Conclusions The similarity in immune complement across a gradient of sociality suggests that a reduced immune repertoire predates the evolution of sociality in bees. The differences in selection on immune genes likely reflect divergent pressures exerted by parasites across social contexts

Test-retest reliability of resting EEG spectra validates a statistical signature of persons

OBJECTIVE: When EEG is recorded in humans, the question arises whether the resting EEG remains stable. We compared the inter-individual variation in spectral observables to the intra-individual stability over more than a year. METHODS: We recorded resting EEG in 55 healthy adults with eyes closed. In 20 persons EEG was recorded in a second session with retest intervals 12-40 months. For electrodes AFz, Cz and Pz alpha peak frequency and alpha peak height were transformed into Z-scores. We compared the curve shape of power spectra by first aligning alpha peaks to 10Hz and then regressing spectra pairwise onto each other to calculate a t-value. The t-value and differences of Z-scores for all pairs of sessions were entered into a generalized linear model (GLM) where binary output represents the recognition probability. The results were cross-validated by out-of-sample testing. RESULTS: Of the 40 sessions, 35 were correctly matched. The shape of power spectra contributed most to recognition. Out of all 2960 pairwise comparisons 99.5% were correct, with sensitivity 88% and specificity 99.5%. CONCLUSIONS: Our statistical apparatus allows to identify those spectral EEG observables which qualify as statistical signature of a person. SIGNIFICANCE: The effect of external factors on EEG observables can be contrasted against their normal variability over time

Test-retest reliability of EEG spectra during a working memory task

The inter-individual variation of EEG spectra is large even for the same cognitive task. We asked whether task-induced EEG spectra remain stable over more than a year. We recorded EEG in 41 healthy adults who performed a modified Sternberg task. In 20 subjects EEG was recorded in a second session with retest intervals 12-40 months. For electrodes AFz, Cz and Pz peak frequency and peak height were determined. We compared the curve shape of power spectra by regressing spectra pairwise onto each other and calculated a t-value. The t-value and pairwise differences in peak frequency and peak height between all sessions were entered into a generalized linear model (GLM) where binary output represents the recognition probability. The results were cross-validated by out-of-sample testing. Of the 40 sessions, 35 were correctly matched. The shape of power spectra contributed most to recognition. Out of all 2400 pairwise comparisons 99.3% were correct, with sensitivity 87.5% and specificity 99.5%. The intra-individual stability is high compared to the inter-individual variation. Thus, interleaved EEG-fMRI measurements are valid. Furthermore, longitudinal effects on cognitive EEG can be judged against the intra-individual variability in subjects

Ultrasound screening program for detection of fetal malformations. Past and current status.

Peer Reviewe